Tricyclo(5,3,1,0{hu 3.8{b )undeca-5,9-dien-2-ones

ABSTRACT

Tricyclo (5,4,0,03,9) undeca-5,10-dien-2-ones and tricyclo (5,4,0,03,8) undeca-5,9-dien-2-ones which are useful in the perfumery art and a process for their preparation from phenols and cyclohexenones.

"United States Patent 1 1 Frater et al.

[ Dec. 2, 1975 TRICYCLO(5,3,1,O )UNDECA-S,9-DIEN- Z-ONES Inventors: Georg Frater, Greifensee; Hans Greuter, Horgen; Hans Schmid, Schwerzenbach, all of Switzerland Assignee: Hoffmann-La Roche Inc., Nutley,

Filed: Apr. 12, 1974 Appl. No.: 460,631

Related U.S. Application Data Division of Ser. No. 300,603, Oct. 25, 1972, Pat. No. 3,836,584.

Foreign Application Priority Data Nov. 21, 1971 Switzerland 16517/71 U.S. Cl. 260/586 G; 131/17; 252/522; 260/586 R; 260/586 C Primary Examiner-Norman Morgenstern Attorney, Agent, or Firm-Samuel L. Welt; Jon S. Saxe; Richard A. Gaither [57] ABSTRACT Tricyclo [5,4,0,0 undeca-5,10-dien-2ones and tricyclo [5,4,0,0 undeca-5,9-dien-2-ones which are useful in the perfumery art and a process for their preparation from phenols and cyclohexenones.

7 Claims, No Drawings wherein R R R R R R,;, R, and R are as above,

TRICYCL(53103'8)UNDECA'SQ'DIEN'Z'ONES and the dotted bond can be optionally hydrogenated.

This is a division of application Ser. No. 300,603 filed Oct. 25, 1972, now US. Pat. No. 3,836,584, entitled DETAlLED DESCRIPTION OF THE INVENTlON uTRlCYCuC KETONESH' As used in this application, the expression lower al- SUMMARY OF THE INVENTION kyl includes both straight-chain and branched-chain hydrocarbon groups containing 1-6 carbon atoms such as methyl, ethyl, propyl, isopropyl, pentyl, 3-pentyl and 10 the like. The alkyl moieties in the lower alkoxy 4 groups are of the same kind. The expression lower alkenyl includes both straight-chain and branchedchain hydrocarbon groups containing 2-6 carbon atoms such as vinyl, allyl, butenyl, pentenyl and the like. The expression halogen includes fluorine, chlorine, bromine and iodine.

Preferred tricyclic ketones of formulae l-A and I-B above are those in which R R and R each represent a lower alkyl group, preferably a methyl group. Also preferred are those compounds wherein R,, R and R are lower alkyl, particularly methyl and those compounds where R,, R R and R are lower alkyl, particularly methyl. Especially preferred tricyclic ketones are:

This invention relates to tricyclo ketones selected from the group consisting of the formula:

and l,3,6-trimethyl-tricyc1o[5,4,0,0 ]undeca-5 l O-dien- 2-one;

1,3 ,6-trimethyl-tricyclic 5 ,3, l ,0 ]undeca-5,9-dien- 2-one;

1,3, l 0-trimethyl-tricyclo[5 ,4,O,0 ]undeca-5, 1 O-dien- 2 one;

1,3,9-trimethyl-tricyclo[ 5 ,3,1 ,O ]undeca-5 ,9-dien- 2-one;

1 ,3,6,10-tetramethyl-tricyclo[5,4,0,0 ]undeca-5,l0-

dien-2-one;

1,3 ,6,9-tetramethyl-tricyclo[5 ,3 ,1 ,0 '"]undeca-5 ,9-

, 3 dien-Z-one;

l,3,6-trimethyl-tricyclo[5,3,l,0 lundecan-2-one;

, 1.1 l,3,l0-trimethyl-tricyclo[5,4,0,0 ]undecan-2-one;

40 l,3,6-trimethyl-tricyclo[5,4,0,0 ]undecan-Z-one; and

l,3,9-trimethyl-tricyclo[5,3,l ,0 ]undecan-2-one.

R 7 The compounds of formula 11 above, can be cyclized to form a mixture of compounds of the formula [-A and formula [-8 above by heating the compound of the formula II above. Generally, heating is carried out at a temperature of from 40 to 200 degrees centigrade. In carrying out this reaction, temperatures of from 60 degrees centigrade to 100 degrees centigrade are pre ferred. However, the preferred temperature utilized in this cyclization will depend upon the particular starting material of formula 11 above which is utilized. Therefore, the preferred reaction temperature depends upon the nature of the substituents R R R R R R R,and R in the compounds of the formula 11 above and the particular solvent. For instance, when R in the starting material of formula II is methyl, better yields can be obtained in a shorter time than with the analo- R R gous compound of formula 11 where R is hydrogen. 5 4 2 The same is true for the reaction temperature. Thus,

H4 II for best results in terms of yields, a decrease of the re- 3 action time can be dispensed with in favor of a reduction of the reaction temperature. Also increasing the pressure will decrease the reaction time necessary to obtain optimum yields of the compounds of the formu- R I lae I-A and l-B.

8 While reaction temperatures of 40 degrees centigrade to about 200 degrees centigrade are generally 1 utilized, the reaction can also take place at temperawherein R R and R are independently selected from the group consisting oflower alkyl, hydrogen and lower alkoxy; R is a hydrogen atom, lower alkyl or lower alkenyl; R and R are independently selected from the group consisting of hydrogen or lower alkyl; R and R are independently lower alkyl; and wherein the dotted bond can be optionally hydrogenated. 50

The compounds of formula I above have a camphorlike, woody, earthy and fatty odor. The compounds of formula I above and their acid addition salts because of their fragrance are useful in the preparation of perfumes, colognes and other scented compositions.

The compounds of formula I-A and l-B can be prepared from compounds of the formula:

tures below 40 degrees centigrade. However, at temperatures below 40 degrees centigrade, the velocity of the reaction is slow requiring long reaction times. Thus, the utilization of temperatures below 40 degrees centigrade makes the process not practical for large scale purposes.

The compounds of formulae LA and 1-8 are formed from the compounds of the formula II by heating the compounds of the formula II in an inert organic solvent. ln carrying out this reaction, any conventional inert organic solvent can be utilized. Generally, it is preferred to utilize inert organic solvents boiling above 40 degrees centigrade. Among the preferred inert organic solvents are hydrocarbons such as hexane, octane, decane, benzene, toluene, etc.; halogenated hydrocarbons such as chloroform, methylenechloride, carbontetrachloride and chlorobenzene; ethers such as dioxane, tetrahydrofuran and anisole; amines such as aniline, dimethylaniline, triethylamine, pyridine, and quinoline; amides such as dimethylformamide, tetramethylurea or hexamethylphosphoric acid triamide; nitriles such as benzonitrile, acetonitrile, etc.; esters such as ethylacetate, butylacetate, etc.; ketones such as acetone, diethylketone and cyclohexanone; or a similar inert organic solvent such as dimethylsulfoxide, tetrahydrothiophene dioxide. When a low-boiling solvent is used, heating is conveniently carried out in an autoclave or a bomb tube so that the temperature can be raised in order to avoid unnecessary long reacting times.

In carrying out this reaction, it is generally best to avoid temperatures above 200 degrees centigrade. This is true since at high temperatures decomposition of the starting material and/or the product can set in.

If desired, the process can be carried out in the presence of a Lewis acid. Any conventional Lewis acid can be utilized in carrying out the process Examples of Lewis acids which can be used are the protons, aluminum chloride, zinc chloride, tin tetrachloride, antimony chloride, iron trichloride, boron trifluoride, boron trifluoride etherate, etc. It is frequently advantageous to use as the proton donator a phenol corresponding to the starting material of formula II.

By heating the compound of formula ll, a mixture of the compound of the formulae l-A and LB is formed. The separation of this mixture into the individual components can be carried out by conventional means such as chromatography. Any conventional method of chromatography can be utilized to carry out this separation. A preferred method is by chromatography on silica gel with hexane/ethyl acetate (8:2 parts by volume) being an especially preferred elution agent. The mixture can also be separated by distillation. Any conventional method of distillation such as distillation in a high vacuum can be utilized. The tricyclic ketone of formula I-B can be obtained in pure form by crystallization from saturated hydrocarbons such as pentane or hexane. It is preferred to carry out the chromatography or distillation step after the major amount of the tricyclic ketone of formula l-B has been crystallized. By this procedure of crystallization, an enrichment of the tricyclic ketone of formula l-A in the mixture is accomplished prior to preparation by chromatography or distillation.

Where the tricyclic ketone of formula I-A or formula l-B contains at least one double bond, this compound may. if desired, be hydrogenated in the presence of a noble metal catalyst. Any conventional noble metal hydrogenation catalyst can be utilized for this purpose. In

carrying out this hydrogenation, the appropriate tricyclic ketone of formula l-A or formula I-B can be dissolved in an inert organic solvent, and the mixture treated with a noble metal catalyst. Any conventionaI inert organic solvent can be utilized for this purpose Among the preferred noble metal hydrogenation catalysts are included platinum oxide, platinum black, mix tures of platinum oxide and platinum black, rhodium alone or on a support such as carbon or aluminum ox ide. Especially preferred as a catalyst for use in thi: process is palladium, alone or on a support such as car bon. The hydrogen is introduced in the usual manne1 and the hydrogenation terminated after the uptake 0 one or two moles of hydrogen. If the hydrogenation o a tricyclic ketone of formula [-8 is interrupted after the uptake of one mole of hydrogen, then only the double bond in the 10,] l-positions will have been saturated.

The compounds of formula II are prepared by reacting an alkali metal salt of a phenol of the formula:

pit

R 5 III wherein R R and R are as above; and X is chlorine, bromine, iodine or aryl sulfonyloxy or lower alkyl sulfonyloxy.

In carrying out this reaction, any conventional inert organic solvent can be used as the reaction medium. Among the preferred inert organic solvents are included aromatic hydrocarbons such as benzene, chlorobenzene and toluene. Among conventional inorganic bases which can be utilized to form the salt of compound III are included alkali metals such as sodium and potassium, and alkali metal hydrides such as sodium hydride.

According to a preferred embodiment of car rying out this reaction a phenol of formula III is dissolved, for example, in benzene and the solution treated with sodium hydride. After salt-formation has occurred, a compound of formula IV is introduced and the mixture is stirred for several hours at a temperature between 0 degrees centigrade and 40 degrees centigrade. Thereafter, the reaction mixture is poured on to water and shaken out with a strong base in order to remove the phenolic constituents. The organic phase is evaporated and the residue purified in the usual manner. As will be evident from the foregoing, the symbol X in formula lV stands for a leaving atom or group. Preferably, X stands for a bromine atom or a tosyloxy or mesyloxy group.

The sterochemistry (cis/trans isomerism) of the sidechain in a compound of formula II is not critical. All isomers can be used as the starting material.

Compounds of formula [1 in which the bond denoted by the broken line is hydrogenated need not be isolated but are used directly in situ as the starting material.

The tricyclic ketones of formulae l-A and l-B provided by the present invention possess particular odorant properties, their odor being camphor-like, woody, earthy and fatty.

The compounds of formulae l-A and I-B are utilized to impart fragrance to various materials such as cosmetics, perfume oils, soaps, lotions, detergents, etc. These compounds are incorporated into various materials in olfactory amounts to impart a fragrance to the material. Also, these scented compositions can contain conventional perfume carriers and perfume diluents. Any conventional perfume carrier and perfume diluent can be utilized in preparing scented compositions in accordance with this invention.

The tricyclic ketones of formulae I-A and I-B can be used in the manufacture of a wide variety of odorant compositions. They can be used, in particular, as components of perfume bases for modern lines (e.g., for bases of hay-, tobaccoor honey-like character) as well as for fougere, chypre and lavender bases. Furthermore, the character of compositions having, for example, flower notes, especially hyacinth, gardenia, violet and lavender notes, can be altered or intensified with the aid of the present tricyclic ketones. These tricyclic ketones harmonize well in compositions with coumarins, ionones and rate wood essences such as vetiver oil, sandalwood oil or patchouli oil. the tricyclic ketones of formulae l-A and l-B also possess fixative properties. The

The amounts in which the tricyclic ketones of formulae l-A and I-B can be used in odorant compositions vary within wide limits. In perfume bases they can be used, for example, in amounts of about 2-40 weight percent and in finished products such as perfumes, lotions, etc., they can be present in an amount of from about 1-5 percent. For the perfuming of technical products (e.g., solid and liquid detergents, synthetic washing agents, aerosols or cosmetic products of all kinds suchas soaps), there can in general be used about 0.1-0.3 weight percent (in the case of washing agents) or about 0.8-2 percent (in the case of soaps) of such perfume bases.

Accordingly, it will be appreciated that the present invention also includes within its scope an odorant composition which contains as an essential odorimparting ingredient or essential odor-imparting ingredients one or more of the tricyclic ketones of formula I-A and/or formula I-B hereinbefore. Further, this invention also includes a method of imparting an odor to materials by applying thereto or incorporating therein an odor-imparting amount of one or more of the tricyclic ketones of formulae I-A and/or l-B hereinbefore or an odorant composition as hereinbefore defined.

The following examples are illustrative but not limitative of the invention. All temperatures are in degrees centigrade.

EXAMPLE 1 5 g of 6- (3-methyl-penta-2,4-dienyl)-2,6-dimethylcyclohexa-2,4-dien-l-one are dissolved in 25 ml of benzene and treated with 5 g of 2,6-dimethylphenol. The mixture is heated at reflux for 6 hours. After cooling to room temperature, the mixture is shaken portionwise with a solution of 36 g of potassium hydroxide, 25 ml of water and 100 ml of methanol. The organic phase is concentrated and theresidue distilled at 7090C/0.03 mmHg. The distillate contains 1,3,6-trimethyl-tricyclo[5,4,0,0 ]undeca-5 ,9-dien-2-one and 1,3 ,6- trimethyl-tricyclo[5,3,l,0 ]undeca-5,9-dien-2-one in the approximate proportion of 3:1 parts by volume.

The 3:1 mixture is dissolved in equal parts by volume of hexane and cooled to 30C. The first-named solid tricyclic ketone separates out to a large extent with scratching. Concentration of the filtrate and repetition of this operation yields further crystals of this tricyclic ketone. The composition of the mixture of the aforementioned tricyclic ketones thereby changes from 3:1 parts by volume to approximately 1:3 parts by volume. The ultimate separation is carried out by chromatography on silica gel using hexane/ethyl acetate (8:2 parts by volume) as the elution agent. There are thus obtained l,3,6-trimethyl-tricyclo[5,4,0,0 ]undeca-5,lO- dien-2-one of melting point 54-55C and 1,3,6- trimethyl-tricyclo[5,3,l,0 lundeca-5,9-dien-2-one of boiling point 7075C/0.03 mmHg.

EXAMPLE 2 By the procedure of Example 1: 6-(penta-2,4-dienyl)-2,4,6-trimethyl-cyclohexa-2,4- dien-l-one is converted to 1,3,10-trimethyl-tricyclo[5,4,0,0 ]-undeca-5,l0-dien-2-one of melting point 49-50C and 1,3,9-trimethyl-tricyc1o[5,3,1,0 ]undeca-5,9-dien-2-one of boiling point 70-75C/0.03 mml-lg (reaction time 48 hours).

EXAMPLE 3 By the procedure of Example 1:

6-(3-methyl-penta-2,4-dienyl)-2,4,6-trimethylcyclohexa-2,4-dien-l-one is converted to l,3,6,l0-tetramethyl-tricyclo[5,4,O,0 ]undeca-5,1O-dien-Z-one of melting point 8386C and l,3,6,9-tetramethyl-tricyclo[5,3,1,0 ]undeca-5,9-dien-2-one of boiling point 7075C/0.03 mmHg (reaction time 12 hours).

EXAMPLE 4 A 1 molar solution of 2,6-dimethylphenol in benzene is treated with sodium hydride and, after completion of the hydrogen evolution, the mixture is treated with a 10 percent molar excess of 3-methyl-penta-2,4-dienyl 1- bromide. After stirring overnight at 0-5C, the reaction mixture is taken up in diethyl ether and shaken with water, 10 percent by weight aqueous potassium hydroxide solution with water. The dried organic phase contains the 6-(3-methyl-penta-2,4-dienyl)-2,6- dimethyl-cyclohexa-2,4-dien-l-one which accures in 8090 percent yield. This dienone can be stored in solution at l 0C, but it is unstable in concentrated form and at higher temperatures. [U.V. in n-hexane: maxima at 2300A (e 22000) and 3050A (e 4270)].

EXAMPLE 5 EXAMPLE 6 By the procedure of Example 4:

2,4,6-trimethylphenol and 3-methy1-penta-2,4-dienyl l-bromide are reacted to form 6-(3-methyl-penta-2,4- dienyl)-2,4,6-trimethyl-cyclohexa-Z,4-dien-l-one:

[U.V. in n-hexane: maxima at 2290 A (e 2350) and 3100 A (e 4400)].

EXAMPLE 7 16 g of l,3,6-trimethyl-tricyclo[5,3,l ,O ]undeca- 5,9-dien-2-one are dissolved in 250 ml of methanol and hydrogenated in the presence of l g of palladium-oncarbon (5 percent). After the uptake of two mols of hydrogen, the mixture is filtered off from the catalyst, evaporated and distilled. The distillate contains 1,3,6- trimethyl-tricyclo[5,3,l,0 lundeca-2-one of boiling point 68-70C/0.05 mmHg. This product is about a 4:1 by volume mixture of the isomers at carbon atom 6.

EXAMPLE 8 By the procedure of Example 7:

1,3, l O-trimethyl-tricyclo[5,4,O,0 ]undeca-5, 1 dien-2-one is converted to l,3,l0-trimethyl-tricyclo[5,4,O,O ]-undecan-2-one of boiling point 6870C/0.05 mmHg.

EXAMPLE 9 By the procedure of Example 7:

1,3 ,6-trimethyl-tricyclo[ ,4',0,0 ]undeca-5 l O-dien- 2-one was converted to l,3,6-trimethy-tricyclo[5,4,0,0' ]undecan-2-one of boiling point 7275C/0.05 mmHg.

EXAMPLE 10 By the procedure of Example 7:

l,3,9-trimethyl-tricyclo[5,3, l ,O -]undeca-5,9-dien- 2-one was converted to l,3,9-trimethyl-tricyclo[5 ,3 ,1 ,0 lundecan-2-one of boiling point 68-70C/0.05 mmHg.

EXAMPLE 1 1 By the procedure of Example 7:

l,3,6-trimethyl-tricyclo[ 5 ,4,0,0 ]undeca-5, l O-dien- 2-one was converted to l,3,6-trimethyl-tricyclo[5,4,0,0 ]undeca-5-en-2-one boiling point 71-73C/0.05 mmHg. However, the hydrogenation was interrupted after the uptake of one mol of hydrogen.

EXAMPLE 12 6.8 g of mesitol dissolved in 50 ml of benzene was treated with 2.4 g of sodium hydride (50 percent suspension in oil). After completion of the salt-formation, 8.5 g of 5-bromo-1-pentene are added thereto. The reaction mixture is heated at reflux for 24 hours, taken up in hexane and shaken with an aqueous potassium hydroxide solution (10 percent by weight) and Claisens alkali (35 g of KOH, 25 ml of water and 100 ml of methanol). The organic phase is dried, evaporated and chromatographed on silicia gel using hexane and 3 percent diethylether in hexane as the elution agent. Evaporation of the eluate and recrystallization of teh residue from hexane yields l,3,9-tri-methyl-tricyclo[5,3,1,0 ]undeca-9-en-2-one of melting point 46-47C.

EXAMPLE 13 The following Example illustrates a typical odorant composition provided by the invention.

Odorant composition (Fougere type) containing l,3 ,6-trimethyl-tricyclo[ 5 ,3 ,l ,O ]undeca-5,9-dien- 2-one.

Sandalwood oil East Indian Sandela Givaudan Coumarin Patchouli oil Vetiver oil Bourbon lsobutyl salicylate Lavender oil cultivated Mousse de chene soluble CF Orange oil ltalian Bergamotte oil Reggio 5 Aldehyde C-l2 MNA l0 percent in phthalic acid diethyl ester Versalide Givaudan Lilial Ciivaudan Aldehyde C-ll undecylenic 1 percent in phthalic acid diethyl ester Geranium oil Bourbon Galbanumoil 1 percent in phthalic acid diethyl ester Ylang ylang oil Bourbon Hydroxycitronellal l,3,6-Trimethyl'tricyclo[5,3,1,0']undeca-S,9- dien-Z-one I000 'isocamphylcyclohexanol l .l ,4,4-tetramethyl 6-ethyl-7-ucetyll .2.3.4-tetrahydronaphlhalene "p-t-hutyl-a-melhylhydrocinnamaldehyde We claim: 1. A compound of the formula:

wherein R,, R and R are independently selected from the group consisting oflower alkyl, hydrogen and lower alkoxy; R is a hydrogen atom, lower alkyl or lower alkenyl; R and R are independently selected from the group consisting of hydrogen or lower alkyl; R and R are independently lower alkyl.

2. A compound of claim 1 wherein R R and R are methyl.

3. The compound of claim 2 wherein said compound is l ,3,6-trimethyl-tricyclo[5,3,1,0 ]undeca-5,9-dien- 2-one.

4. The compound of claim 1 wherein R.,, R and R is methyl.

5. The compound of claim 4 wherein said compound is l,3 ,9-trimethyl-tricyclo[5,3, l ,O ]undeca.-5 ,9-dien- 2-one.

6. The compound of claim 2 wherein said R R R and R are methyl.

7. The compound of claim 6 wherein said compound is 1,3,6,9-tetramethyl-tricyclo[5,3,l ,O ]undeca-5,9- dien-2-one. 

1. A COMPOUND OF THE FORMULA:
 2. A compound of claim 1 wherein R2, R5 and R6 are methyl.
 3. The compound of claim 2 wherein said compound is 1,3,6-trimethyl-tricyclo(5,3,1,03,8)undeca-5,9-dien-2-one.
 4. The compound of claim 1 wherein R1, R5 and R6 is methyl.
 5. The compound of claim 4 wherein said compound is 1,3,9-trimethyl-tricyclo(5,3,1,03,8)undeca-5,9-dien-2-one.
 6. The compound of claim 2 wherein said R1, R2, R5 and R6 are methyl.
 7. The compound of claim 6 wherein said compound is 1,3,6,9-tetramethyl-tricyclo(5,3,1,03,8)undeca-5,9-dien-2-one. 